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Organic cation transporter 1 (OCT1) is a liver-specific transporter and plays an essential role in drug disposition and hepatic lipid metabolism. Therefore, inhibition of OCT1 may not only lead to drug-drug interactions but also represent a potential therapy for fatty liver diseases. In this study, we systematically investigated the inhibitory effect of 200 natural products on OCT1-mediated uptake of 4,4-dimethylaminostyryl

Background Diabetes mellitus has been widely acknowledged to have a negative effect on the osteoblastic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). However, the underlying epigenetic mechanisms associated with this process remain to be elucidated. The goal of the present study was to investigate the effect of diabetes mellitus on the osteoblastic differentiation of BMSCs and assess the role of histone methylation in the observed phenomena.Methods The effect of diabetes mellitus was simulated by isolating BMSCs from diabetic rats and culturing them with glucose and AGEs.Results The osteoblastic differentiation ability of BMSCs was shown to be decreased in diabetes mellitus, as indicated by alkaline phosphatase activity and the mRNA levels of osteoblast-related genes. Furthermore, diabetes mellitus caused an increased expression of the histone methylase EZH2 and the levels of H3K27Me3 and decreased the expression of the histone demethylase KDM6B, as demonstrated by qRT-PCR and western blotting. Furthermore, immunofluorescence staining suggested that both EZH2 and H3K27Me3 were primarily localized in the nucleus. In addition, chromatin immunoprecipitation assays indicated an increased presence of H3K27Me3 on the promoter region of the BMP4 gene. Conclusion We demonstrated that the osteoblastic differentiation of BMSCs is dramatically reduced in diabetes mellitus. In addition, upregulation of EZH2 expression and downregulation of KDM6B expression may not be enough to eliminate transcriptional repression mediated by H3K27Me3 on the promoter region of the BMP4 gene during the osteoblastic differentiation of BMSCs in diabetes mellitus.

Increasing production of corannulene (COR), a non-planar polycyclic aromatic hydrocarbon (PAH) with promising applications in many fields, has raised a concern about its potential toxic effects. However, no study has been undertaken to evaluate its metabolism and toxicity in mammals. In this study, the acute toxicities of COR in mice were compared with benzo[apyrene (BaP), a typical planar PAH with almost the same molecular weight. After 3-day exposures, the concentrations of COR in both plasma and tissues of mice were higher than that of BaP. However, blood chemistry and tissue weight monitoring showed no observable toxicities in COR-exposed mice. Compared to BaP, exposure to COR resulted in less activation of the aryl hydrocarbon receptor (AhR) and thus less induction of hepatic cytochrome P450 1A(CYP1A) enzymes, which play a critical role in metabolism of both COR and BaP. Additionally, COR also elicited less oxidative stress and microbiota alteration in the intestine than did BaP. RNA-seq analysis revealed that liver transcriptomes are responsive to COR and BaP, with less alterations observed in COR-exposed mice. Unlike BaP, exposure to COR had no effects on hepatic lipid and xenobiotic metabolism pathways. Nonetheless, COR appeared to alter the mRNA expressions of genes involved in carcinogenicity, oxidative stress, and immune-suppression. To conclude, this study for the first time unveils a comparative understanding of the acute toxic effects of COR to BaP in mice, and provides crucial insights into the future safety assessment of COR.

Despite numerous studies on the toxicities of planar polycyclic aromatic hydrocarbons (PAHs), very little is known about the toxicological profiles of non-planar PAHs. In the present study, the cytotoxicity of corannulene (COR), a typical bowl-shaped PAH with a myriad of applications in the area of material chemistry, and benzo[a]pyrene (BaP), a typical planar PAH with similar molecular weight, were systematically compared in various cell lines. Compared with BaP, exposure to COR resulted in less cytotoxic responses in both human (HepG2) and murine (Hepa1-6) hepatoma cells, which was characterized with a slower cellular accumulation as well as a weaker induction of cytochrome P450 1 (CYP1/Cyp1) isozymes. Knockdown of aryl hydrocarbon receptor (AhR) by siRNA attenuated the inductive effect of COR on CYP1A/Cyp1a mRNA levels in these two cell lines. Further analysis revealed that derivatization greatly influenced the cytotoxicity of COR, which was positively correlated with their binding affinities to the AhR, as demonstrated by in silico molecular docking. Overall, these results suggest that AhR appears to be involved in the cytotoxic responses of COR and its derivatives, providing a fundamental understanding of the biological effects of bowl-like PAHs.

The influence of Mn on the microstructure and mechanical properties of as-cast and as-solution Mg–Mn alloys was investigated in the present work. X-ray diffraction patterns revealed that the dominant phases of the experimental alloys were the α-Mg matrix and Mn precipitates. The average grain sizes of the as-cast Mg–Mn alloys decreased monotonically with increasing Mn content, although Mn addition showed a negative grain refinement effect on the as-cast Mg alloys. Increasing the Mn content enhanced the tensile yield strength of the as-cast alloys from 17.6 to 35.1 MPa. The improved mechanical properties are mainly attributed to precipitation hardening; a large number of Mn precipitates were located within the matrix and along the grain boundaries. Meanwhile, the lower tensile strength and Vickers hardness of the as-solution alloys is explained by the coarsened microstructure and poor solid-solution strengthening behaviour.

A bioactivity guided program exploring the interaction of phytochemicals in the entire plant Primula macrocalyx with the organic anion transporters (OAT1 and OAT3) and microorganisms led to the elucidation of ten known flavones (1–4, 6–10, 12) and two previously undescribed flavones (5, 11). The structures of the compounds were determined by extensive analysis of spectroscopic data, as well as by comparison with data from previous reports. Two known flavones (9, 12) are reported for the first time from the family Primulaceae. All compounds were evaluated for inhibition of OAT1 and OAT3. Six flavones (2, 3, 6–8, 12) showed potent inhibitory activity on OAT1, while seven flavones (2, 3, 6–9, 12) showed marked inhibitory activity on OAT3, with IC50 ≤ 10.0 µM. Antimicrobial activities of crude fractions against sixteen microorganisms were tested to give a target yeast strain Candida rugosa for further evaluation of MICs on the isolates. Three flavones (7, 8, 12) showed marked antifungal activity with MIC µM. To our knowledge, this study is the first to evaluate these flavones as inhibitors of the OAT1 and OAT3, and as antifungal agents.

In this work, we design a large-range wavelength tunable guided-mode resonance filter (GMRF) based on dielectric grating symmetrically sandwiched by BaK5 substrates. The working wavelength of such a filter can be actively tuned from about 491 nm to 690 nm by changing the incident angle. Besides, the filter shows almost 100% reflection efficiency and narrow bandwidth at the working wavelength, accompanied by almost 0% side-band rejection in a wide range. We offer a simple and efficient way to actively tune the working wavelength of the filter, which may achieve some applications in visible filters.

Yinzhihuang oral liquid (YZH) is a traditional Chinese medicine that has been widely used in Asia to prevent and treat neonatal hyperbilirubinemia, but the published preclinical studies on its anti-hyperbilirubinemia effect are conducted in adult animals, partly due to the lack of preclinical neonatal hyperbilirubinemia animal models. In the present study, we tested six reagents to induce hyperbilirubinemia in neonatal rats, and established two appropriate neonatal hyperbilirubinemia rat models by subcutaneous injection of δ-Aminolevulinic acid (ALA, 200 mg/kg) or novobiocin (NOVO, 200 mg/kg). Oral treatment of YZH (80, 160 and 320 mg/kg) significantly decreased serum conjugated bilirubin levels in ALA-treated neonatal rats and serum unconjugated bilirubin levels in NOVO-treated neonatal rats, respectively. Additionally, pre-treatment of YZH also prevented the increase of serum bilirubin levels in both ALA- and NOVO-treated rats. Mechanistically, YZH significantly up-regulated the mRNA expression of genes involved in hepatic bilirubin disposition (organic anion-transporting polypeptide 1b2, Oatp1b2; multidrug resistance-associated protein 2, Mrp2) and bilirubin conjugation (UDP-glucuronosyltransferase 1a1, Ugt1a1). Additionally, YZH up-regulated the mRNA expression of cytochrome P450 1A1 (Cyp1a1), the target gene of aryl hydrocarbon receptor (AhR), and increased the nuclear protein levels of AhR in livers of neonatal rats. YZH and its two active ingredients, namely baicalin (BCL) and 4'-hydroxyacetophenone (4-HT), up-regulated the mRNA expression of AhR target genes (CYP1A1 and UGT1A1) and increased nuclear protein levels of AhR in HepG2 cells. In conclusion, the present study provides two neonatal hyperbilirubinemia animal models and evaluates the anti-hyperbilirubinemia effect and mechanisms of YZH in neonatal animals.

Excessive production of AGEs in diabetic patients will affect the normal function of osteoblasts, and this process may be related to autophagy of osteoblasts. This study aims to explore the effect of advanced glycation end products (AGEs) on autophagic activity during osteogenic differentiation in rat bone marrow mesenchymal stem cells (BMSCs).BMSCs were isolated and cultured in vitro, treated with different concentrations (0, 50, 100, 200, and 400 mg/L) of AGEs for different time (3, 6, 12, 24, 48, and 72 h). The proliferation activity was detected by CCK-8 method. The mRNA and protein expression levels of Beclin1 and LC3 in cells were detected by real-time PCR and Western blotting, respectively.The autophagic vacuoles were observed under the transmission electron microscope. The cells were treated with autophagy promoter rapamycin or autophagy inhibitor 3MA. After 7 days of osteogenic induction, we performed alkaline phosphatase (ALP) staining and real-time PCR to detect the mRNA expression levels of osteogenesis-related genes.In the low-concentration groups, the proliferation activity in BMSCs was increased (Low concentration of AGEs can enhance the proliferative activity of BMSCs and promote osteogenic differentiation by accelerating autophagy. High concentration of AGEs can suppress the proliferation of BMSCs and inhibit osteogenic differentiation by reducing autophagy.

Enterovirus 71 (EV71) has caused large hand, foot, and mouth disease (HFMD) epidemics among young children, and EV71 infection is the leading cause of severe HFMD cases and deaths. In mainland China, the prevalence and risk factors of non-C4 EV71 strains are still unclear. In this study, we monitored non-C4 strains over a 10-year HFMD epidemiological surveillance period in Xiamen. The 5’UTR and VP1 coding region of EV71 strains were amplified by RT-nested PCR and sequenced. Thirty-two non-C4 EV71 strains were identified during 2009-2018. This study provides important information about the prevalence of EV71 in China that will be applicable for development of vaccines and diagnostic reagents as well as establishment of policies for HFMD prevention and control. Supplementary Information The online version contains supplementary material available at 10.1007/s00705-021-05097-9.

Additional file 1: The PRISMA checklist.

Additional file 4: Forest plot of mouth breathing caused by adenoid/tonsil hypertrophy.

Additional file 5: Forest plot of mouth breathing caused by OSAS.

Additional file 6: Forest plot for children aged 2–10.

Additional file 2: Electronic search strategy for PubMed.

Additional file 7: Forest plot for children aged 7–14.

Additional file 3: Study selection flow diagram (PRISMA).

Background: Hesperetin, an active compound found in citrus fruits, possesses antiproliferative effects toward several types of cancer cell lines, including cervical cancer. In this study, we explore the antitumor effects of Hesperetin on the human cervical cancer human papilloma virus (HPV)-positive (CaSki and HeLa) and HPV-negative (C-33A) cell lines and further elucidated the underlying mechanisms of this action. Methods: Cell viability and proliferation was measured by the MTT assay and 5-ethynyl-2′-deoxyuridine (EdU) incorporation assay, respectively. dUTP-fluorescein nick end-labeling (TUNEL) staining, Annexin V‑fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining and flow cytometry was used to assess the degree of apoptosis. JC-1 staining assay was used to evaluate the change of mitochondrial membrane potential (ΔΨm) and Western blot assays were used to determine apoptosis-related factors at protein level. Results: Hesperetin (100, 200 and 400 μM) exhibited a significant exclusive inhibitory effect against the growth of HPV-infected CaSki and HeLa cancer cells via induction of apoptosis in a concentration-dependent manner, while it was almost not active in HPV-negative C-33A cancer cells and normal cervix epithelial H8 cells. Moreover, this antitumor effect executed by Hesperetin was associated with disruption of ΔΨm, the release of cytochrome c from mitochondria, activation of pro-apoptotic proteins (Bax, cleaved caspase-3 and caspase-9) and inhibition of anti-apoptotic proteins (Bcl-2). During this process, cleaved caspase-8 remained unchanged. In addition, Hesperetin led to a downregulation of E6 oncoprotein expression and upregulation of tumor suppressor protein p53 level. Conclusions: Collectively, these results implicated that Hesperetin can induce apoptosis of HPV‑positive cervical cancer cells via a mitochondria-mediated intrinsic signaling pathway, together with the repression of E6 and enhancement of p53 protein level, indicating Hesperetin may be considered as a potential candidate for the development of innovative anti-HPV cervical cancer agents.

To explore the difference in odontoblast differentiation capacity between stem cells from human exfoliated deciduous teeth (SHED) and dental pulp stem cells (DPSCs), and to examine the expression level of ephrinB1 in odontoblast differentiation of these stem cells.The stems cells were divided into a SHED group and a DPSCs group. After odontoblast differentiation induction, the above 2 groups were also randomly divided into a 3 d group and a 7 d group, respectively.The calcium deposition was detected by alkaline phosphatase (ALP) staining and alizarin red staining.The mRNA and protein expressions of ephrinB1, dentin matrix protein-1 (DMP-1) and dentin sialophosphoprotein (DSPP) were detected by real-time PCR and Western blotting.ALP staining and alizarin red staining showed that there was stronger mineralization capacity in the SHED group than that in the DPSCs group. The relative mRNA and protein expressions of DMP-1, DSPP, and ephrinB1 in the SHED group were higher than those in the DPSCs group except for the protein expression of DMP-1 in the SHED 3 d group (allSHED has stronger odontoblast differentiation capacity than DPSCs. In addition, ephrinB1 may be involved in the processes of odontoblast differentiation in the SHED and DPSCs.

The current coronavirus disease 2019 (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a public health emergency of international concern. There has been a surge in demand for COVID-19 diagnostic reagents, as timely detection of virus carriers is one of the most important components of disease prevention and control. Nucleic acid testing (NAT), with high sensitivity and specificity, is considered the "gold standard" for the diagnosis of COVID-19. Therefore, more than 700 research units and companies have been devoted to developing NAT reagents. To date, nearly 600 research units and companies have claimed to have completed the development of NAT reagents. The use of these products has a positive effect on disease prevention and control; however, exaggerated claims and inadequate understanding of the products have led to improper access to reagents and equipment in clinics. This has resulted in chaos in the clinical diagnosis of COVID-19. Herein, we have overviewed the COVID-19 NAT products, including their principles, corresponding advantages and disadvantages, relevant circumstances for application, and respective roles in epidemic containment. Our comments may provide some references for assay developers and aid clinical staff in choosing the appropriate class of test from the different tests available.

Knowledge of the host immune response after natural SARS-CoV-2 infection is essential for informing directions of vaccination and epidemiological control strategies against COVID-19. In this study, thirty-four COVID-19 patients were enrolled with 244 serial blood specimens (38.1% after hospital discharge) collected to explore the chronological evolution of neutralizing (NAb), total (TAb), IgM, IgG and IgA antibody in parallel. IgG titers reached a peak later (approximately 35 days postonset) than those of Nab, Ab, IgM and IgA (20∼25 days postonset). After peaking, IgM levels declined with an estimated average half-life of 10.36 days, which was more rapid than those of IgA (51.25 days) and IgG (177.39 days). Based on these half-life data, we estimate that the median times for IgM, IgA and IgG to become seronegative are 4.59 (IQR 4.12-5.03), 7.78 (IQR 6.71-9.16) and 42.72 (IQR 33.75-47.96) months post disease onset. The relative contribution of IgM to NAb was higher than that of IgG (standardized β regression coefficient: 0.53 vs 0.48), so the rapid decline in NAb may be attributed to the rapid decay of IgM in acute phase. However, the relative contribution of IgG to NAb increased and that of IgM further decreased after 6 weeks postonset. It’s assumed that the decline rate of NAb might slow down to the same level as that of IgG over time. This study suggests that SARS-CoV-2 infection induces robust neutralizing and binding antibody responses in patients and that humoral immunity against SARS-CoV-2 acquired by infection may persist for a relatively long time.

The effect of titanium on the microstructure, the texture, and the mechanical properties of as-extruded Mg–Sn alloy has been investigated in the present work. The result reveals that the alloy subjected to the optimized extrusion process shows an extremely refined microstructure with an average grain size of 1.7 μm. Meanwhile, the addition of titanium has an obvious effect on intensifying the basal texture where the basal slip cannot be easily activated during tensile testing. As a result, the alloy shows excellent mechanical properties where yield strength and elongation are 200 MPa and 30.2%, respectively. The enhanced yield strength of the alloy can be attributed to the extremely refined microstructure and the intensified basal texture, while the improved elongation of the alloy can be explained by the ultra-fine-grained microstructure through reducing the critical resolved shear stress that favors the prismatic slip activity to accommodate the basal slip.

BACKGROUND: Mouth breathing is closely related to the facial skeletal development and malocclusion. The purpose of this systematic review and meta-analysis was to assess the effect of mouth breathing on facial skeletal development and malocclusion in children. METHODS: An electronic search in PubMed, the Cochrane Library, Medline, Web of Science, EMBASE and Sigle through February 23rd, 2020, was conducted. Inclusion criteria were children under 18 years of age with maxillofacial deformities due to mouth breathing. Methodological quality assessments of the selected articles were performed using the Newcastle-Ottawa Scale. The risk of bias in nonrandomized studies of interventions (ROBINS-I) tool for controlled clinical trials. The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach was used for the quality assessment. The included indicators were SNA, SNB, ANB, SN-OP, SNGoGn, MP-H, 1-NA, 1. NA, 1. NB, 1-NB, SPAS, PAS, and C3-H. Data concerning the mean difference in mesial molar movement and extent of canine retraction were extracted for statistical analysis. The mean differences and 95% confidence intervals were analyzed for continuous data. Review Manager 5.3, was used to synthesize various parameters associated with the impact of mouth breathing on facial skeletal development and malocclusion. RESULTS: Following full-text evaluations for eligibility, 6 studies were included in the final quantitative synthesis. In Sagittal direction, SNA (MD: -1.61, P

Introduction Iron accumulates in the brain during aging, which catalyzes radical formation, causing neuronal impairment, and is thus considered a pathogenic factor in Alzheimer's disease (AD). To scavenge excess iron-catalyzed radicals and thereby protect the brain and decrease the incidence of AD, we synthesized a soluble pro-iron 5-YHEDA peptide. However, the blood-brain barrier (BBB) blocks large drug molecules from entering the brain and thus strongly reduces their therapeutic effects. However, alternative receptor- or transporter-mediated approaches are possible. Methods A low-density lipoprotein receptor (LDLR)-binding segment of Apolipoprotein B-100 was linked to the 5-YHEDA peptide (bs-5-YHEDA) and intracardially injected into senescent (SN) mice that displayed symptoms of cognitive impairment similar to those of people with AD. Results We successfully delivered 5-YHEDA across the BBB into the brains of the SN mice via vascular epithelium LDLR-mediated endocytosis. The data showed that excess brain iron and radical-induced neuronal necrosis were reduced after the bs-5-YHEDA treatment, together with cognitive amelioration in the SN mouse, and that the senescence-associated ferritin and transferrin increase, anemia and inflammation reversed without kidney or liver injury. Discussion bs-5-YHEDA may be a mild and safe iron remover that can cross the BBB and enter the brain to relieve excessive iron- and radical-induced cognitive disorders.

OBJECTIVE: To explore the effect of advanced glycation end products (AGEs) on osteoclasts at different stages of differentiation. METHODS: Raw264.7 cells cultured in vitro were induced for osteoclastogenesis using RANKL, and the stages of differentiation of the osteoclasts were determined with TRAP staining. The cells were then randomly divided into control group, early-stage AGEs intervention group and late-stage AGEs intervention group. The viability of the cells after AGEs treatment was assessed using CCK-8 method. The cells were examined after the induction for osteoclastogenesis using TRAP staining, and the expression levels of RANK, NFATC-1, TRAF-6, TRAP and CTSK mRNAs were tested with RT-PCR; the expressions of CTSK and RANK proteins were detected using Western boltting. RESULTS: We defined the initial 3 days of induction as the early stage of differentiation and the time beyond 3 days as the late stage of differentiation of Raw264.7 cells. Intervention with AGEs at 100 mg/L produced no significant effects on the viability of the cells, but AGEs suppressed the cell proliferation at a concentration exceeding 100 mg/L. The number of osteolasts in the early- and late-stage intervention groups was greater than that in the control group, but the cell count differed significantly only between the early-stage intervention group and control group (P < 0.05). The gene expressions of RANK, NFATC-1, TRAF-6, TRAP and CTSK all increased after the application of AGEs in both the early and late stages of differentiation, but the changes were significant only in the early-stage intervention group (P < 0.05). The changes in CTSK and RANK protein expressions were consistent with their mRNA expressions. CONCLUSION: AGEs can affect the differentiation of osteoclasts differently when applied at different stages, and intervention with AGEs at the early stage produces stronger effect to promote osteoclast differentiation than its application at a late stage.

Organic anion transporters 1 and 3 (OAT1 and OAT3) play a critical role in renal drug-drug interactions and are involved in the nephrotoxicity of many anionic xenobiotics. To date, relatively little is known about the interaction of natural compounds with OAT1 and OAT3. Of the 270 natural compounds screened in the present study, 21 compounds inhibited OAT1 and 45 compounds inhibited OAT3. Further concentration-dependent studies identified 7 OAT1 inhibitors and 10 OAT3 inhibitors with IC50 values of

Objective — To systematically evaluate the clinical efficacy of metformin combined with chemotherapy in the treatment of patients with ovarian cancer. Methods — Methods: Search Pubmed, Embase, Web of science, Cochrane Library database, and screen the literature of randomized controlled trials and cohort studies of metformin combined with chemotherapy in the treatment of ovarian cancer, and use Revman5.2 software to conduct meta-analysis to compare metformin combined with chemotherapy (experimental Group) or chemotherapy alone (control group) for the treatment of ovarian cancer. Results — A total of 389 articles were retrieved, and 4 cohort studies and 2 randomized controlled trials were screened and included, involving 2010 patients with ovarian cancer. Compared with the control group, the overall survival rate of metformin combined with chemotherapy in patients with ovarian cancer (HR=0.55, 95% confidence interval 0.34-0.89, P=0.01, I2=36%), progression-free survival rate (HR=0.43, The 95% confidence interval 0.20-0.96, P=0.04, I2=42%) and disease-free survival rate (HR=0.24, 95% confidence interval 0.11-0.50, P=0.0001) were significantly better than the control group. Conclusion — Metformin combined with chemotherapy can significantly improve the therapeutic effect of patients with ovarian cancer.

Emodin is an active ingredient in many herbal medicines and has a broad spectrum of pharmacological activities. The current data indicate that emodin exerts its beneficial effect on alpha-naphthylisothiocyanate (ANIT)-induced intrahepatic cholestasis through its anti-oxidant and anti-inflammatory activities. Emodin has little effect on the concentrations of bile acids (BAs) in livers of ANIT-treated mice. Instead, emodin shows a potential pro-cholestatic effect by interfering with the crosstalk between AMP-activated protein kinase (AMPK) and farnesoid X receptor (Fxr) in the liver, which leads to a suppression of bile salt export pump (Bsep). Two emodin-containing herbs, namely Polygonum multiflorum (PM) and Semen cassiae (SC), markedly aggravate the intrahepatic cholestasis in ANIT-treated mice. SC interferes with the AMPK-Fxr crosstalk and suppresses Bsep in livers of mice. ANIT markedly increases the hepatic retention of emodin in SC-treated mice. The major SC constituents, in particular three anthraquinones, are able to activate AMPK in HepG2 cells and inhibit Bsep in primary mouse hepatocytes, with emodin showing the strongest activities. Together, the present study identifies a potential pro-cholestatic role of emodin in the hepatotoxicity of herbs.

Background Malignant pleural effusion is a common complication of non-small cell lung cancer (NSCLC); however, treatment options remain limited. This study evaluated the safety and efficacy of sequential intrapleural therapy with lobaplatin and erythromycin for NSCLC-mediated malignant pleural effusion. Methods Fifty-six patients with NSCLC complicated with malignant pleural effusion were recruited for a prospective single-arm study from December 2014 to 2016; one patient dropped out. In addition to conventional systemic chemotherapy, lobaplatin and erythromycin were intrapleurally injected into subjects. Short and long-term responses were analyzed. The concentration of ultrafilterable platinum in the pleural effusion and plasma were detected at different time points. Incidences of severe adverse reactions were observed. Results In the 55 evaluable patients, the effective rate of pleural effusion was 81.8% after six weeks of treatment. Six and twelve months after treatment, the effective rates were 60% and 21.8%, respectively, and the one-year survival rate was 83.6%. The concentrations of lobaplatin in pleural effusion and plasma two hours after injecting 50 mg lobaplatin into the thoracic cavity were 13.763 ± 1.523 μg/mL and 1.120 ± 0.164 μg/mL, and 17 hours later were 1.961 ± 0.351 μg/mL and 0.578 ± 0.095 μg/mL, respectively. The rate of severe adverse reactions of the first cycle of systemic chemotherapy combined with lobaplatin and erythromycin did not significantly differ from the rate in the second cycle. Conclusion Intrapleural combination therapy with lobaplatin and erythromycin is a safe and efficient treatment for patients with NSCLC-mediated malignant pleural effusion.

Because of the special crystallization structure (hexagonal close-packed structure), it is difficult to achieve the synergy between strength and ductility in Mg alloys. High strength can be obtained through alloying addition or low-temperature deformation, but these methods usually cause the extremely poor ductility (less than 5%). Meanwhile, solid solution treatment or considerable alloying addition, such as RE, Li, can probably possess the superior ductility, whereas these techniques commonly result in the insufficient strength (poor than 100 MPa). However, Mg 1Mn binary alloy developed in our previous work extruded at a low temperature exhibiting the superior ductility (38.8%) with medium yield strength (204.3 MPa) has been recommended as one of the candidates to improve the strength-ductility synergy in Mg alloys. In this paper, a low-alloyed Mg-1Mn-1Al alloy has been developed to overcome the disequilibrium between strength and ductility. The alloy has a superior elongation capacity (~ 32%) and a reasonably high tensile yield strength (~ 280 MPa) at room temperature. The reasonably high yield strength of the alloy can be dominantly attributed to the refined DRXed grains based on the Hall-Petch relationship, intensified basal texture leading to the basal slip activity difficultly, a great number of nano-scaled Al8Mn5 secondary particles pinning the dislocation motion through the dispersion hardening and the multi-heterogeneous microstructure inducing bask-stress strengthening as dislocation pile-up. The superior elongation capacity of the alloy can be mainly explained as the ultra-fined microstructure through reducing the critical resolved shear stress (CRSS) ratio between prismatic slip and basal slip that favors prismatic slip activity to accommodate basal slip.

In this paper, the effect of aluminium on microstructure and mechanical properties of as-cast magnesium–manganese alloy has been investigated by means of X-ray diffraction, optical microscopy and scanning electron microscopy. The results reveal that various Al–Mn intermetallic compounds form with an increase of Al content. As a result, microstructure of AM11 alloy has been effectively refined due to the formation of Al8Mn5 phase along the grain boundary, while Al addition is explained as the main reason on refining the microstructure of AM91 alloy due to its higher grain growth restriction factor value of ∼4.32. The tensile yield strength (TYS) has been improved steadily from 27.4 to 122.9 MPa with increasing Al content, because of the combined effects of grain boundary strengthening, solid solution strengthening and precipitation hardening behaviours.

We design a broadband polarization beam splitter (PBS) operating in the terahertz (THz) communication band 0.1THz-1.2THz. The transmittance of the TM mode is larger than 95%, in the meanwhile, the extinction ratio can even reach 49dB. Considering the unavoidable deformation in grating fabrication, we also check the performance of the PBS based on trapeziform grating. Results show that increasing the duty cycle while the slope angle diminishing can effectively increase the TM mode transmittance and the extinction ratio, which can compensate the affection induced by the geometric deformation. This design may achieve some potential applications in THz manipulation system.

The distribution of water channels in the crystal morphology of type-α hemi-hydrated gypsum (α-HH) was theoretically detected to investigate the effect of water channels on the hydration reactivity of hemi-hydrate phosphogypsum (HPG). Results showed that water channels were mainly distributed in the cylinders of α-HH crystal, whereas no water channel existed in the conical surfaces parallel to the z -axis. Increasing the number of water channels was critical to enhance the hydration activity of HPG compared with the hydration reactivity of industrial HPG and type-α high-strength gypsum. Controlling the technological parameters of crystallization by concentration of liquid-phase SO 4 2 − made it possible to obtain HPG which had the stumpy crystals of α-HH and high hydration reactivity.

SARS-CoV-2 has caused COVID-19 pandemic globally in the beginning of 2020, and qualitative real-time RT-PCR has become the gold standard in diagnosis. As SARSCoV-2 with strong transmissibility and pathogenicity, it has become a professional consensus that clinical samples from suspected patients should be heat inactivated at 56°C for 30 min before further processing. However, previous studies on the effect of inactivation on qualitative real-time RT-PCR were conducted with diluted samples rather than clinical samples. The aim of this study was to investigate whether heat inactivation on clinical samples before detection will affect the accuracy of qualitative real-time RT-PCR detection. All 46 throat swab samples from 46 confirmed inpatients were detected by qualitative real-time RT-PCR directly, as well as after heat inactivation. Heat-Inactivation has significantly influenced the qualitative detection results on clinical samples, especially weakly positive samples. The results indicate the urgency to establish a more suitable protocol for COVID-19 clinical sample's inactivation.

Organic anion transporters (OATs in humans, Oats in rodents) play an important role in the distribution and excretion of numerous endogenous metabolic products and exogenous organic anions, including a host of widely prescribed drugs. Their ligand recognition is also important for drug therapy and development. In this study, the n-butanol and dichloromethane soluble fractions of Juniperus oblonga were found to inhibit OAT3 in vitro and three biflavonoids were found to be responsible for this activity. One of these compounds, amentoflavone exhibited stronger inhibition than probenecid, a known strong inhibitor of OAT3. Biological characterization of amentoflavone in vivo also showed inhibition of Oat3. Preliminary observations of structure-activity relationships suggest that the biflavonoids are more potent inhibitors of this transporter than their corresponding monomer, and that methylation of even a single hydroxyl group results in a substantial decrease in activity. This greater potency of the biflavonoids may indicate the need for a more in-depth investigation of the distribution of biflavonoids in plants used as foodstuffs and herbal medicines, due to their potential for causing interactions with OAT3 substrate drugs.

Background Malignant pleural effusion is a common complication of non‐small cell lung cancer (NSCLC); however, treatment options remain limited. This study evaluated the safety and efficacy of sequential intrapleural therapy with lobaplatin and erythromycin for NSCLC‐mediated malignant pleural effusion. Methods Fifty‐six patients with NSCLC complicated with malignant pleural effusion were recruited for a prospective single‐arm study from December 2014 to 2016; one patient dropped out. In addition to conventional systemic chemotherapy, lobaplatin and erythromycin were intrapleurally injected into subjects. Short and long‐term responses were analyzed. The concentration of ultrafilterable platinum in the pleural effusion and plasma were detected at different time points. Incidences of severe adverse reactions were observed. Results In the 55 evaluable patients, the effective rate of pleural effusion was 81.8% after six weeks of treatment. Six and twelve months after treatment, the effective rates were 60% and 21.8%, respectively, and the one‐year survival rate was 83.6%. The concentrations of lobaplatin in pleural effusion and plasma two hours after injecting 50 mg lobaplatin into the thoracic cavity were 13.763 ± 1.523 μg/mL and 1.120 ± 0.164 μg/mL, and 17 hours later were 1.961 ± 0.351 μg/mL and 0.578 ± 0.095 μg/mL, respectively. The rate of severe adverse reactions of the first cycle of systemic chemotherapy combined with lobaplatin and erythromycin did not significantly differ from the rate in the second cycle. Conclusion Intrapleural combination therapy with lobaplatin and erythromycin is a safe and efficient treatment for patients with NSCLC‐mediated malignant pleural effusion.